Having completed a decade of work on antiviral treatment of genital herpes, we turned last year to studies of disease prevention. We began with phase I assessment of a new recombinant HSV-2 glycoprotein D vaccine in alum. We recruited 24 adults, some with and without prior HSV-1 and/or 2 infection. Vaccinations of 30ug or 100ug were given at 0, 1, 2, and 12 months and were associated with minimal local or systemic reactions. ELISA titers to gD and gB, neutralizing antibodies to HSV2 and lymphocyte blastogenesis are being tested serially . By 18 months of study we've shown excellent primary immune responses to gD and marked (7-15 fold) boosts of titers in previously infected subjects. On the basis of these excellent responses we enrolled 40 patients with recurrent genital herpes into a placebo-controlled vaccine trial in collaboration with the Univ. of Washington. The goal is to determine whether boosted immunity leads to less frequent recurrences. In the coming year we will complete these studies and begin to explore adjuvants and vaccinations with gB and gD.